The treatment of peripheral T-cell lymphomas (PTCLs) remains a significant challenge. Barriers to more rapid progress in understanding and treating T-cell lymphomas include the relatively low incidence of each PTCL subtype, limited clinical trial enrollment and sample availability, heterogeneity across PTCL subtypes, and a lack of model systems. The overall goal of Core B is to provide essential human and murine reagents for the performance of each of the projects. Our clinical trial network now includes 11 major academic institutions across the United States. This network works cooperatively to efficiently accrue early-phase clinical trials investigating many of the most promising treatment strategies for PTCL. An essential component of these clinical trials is the collection of adequate biospecimens that are passed through an established pipeline for characterization, banking, xenografting and other uses. The intention is to ensure that maximum discovery of predictive biomarkers and mechanisms of resistance are enabled with these precious resources. Results from those assays are used to guide the next generation of clinical trials in an iterative fashion, either by informing patient selection through a predictive biomarker or by driving the development of combination strategies that overcome resistance. At the same time, our patient-derived xenograft (PDX) repository now includes >60 PTCL PDXs. These models are extensively characterized, banked and distributed to investigators around the world through an open-source repository. All available PTCL cell lines have also been organized within the Samples and Models Core, characterized by exome and transcriptome sequencing, copy number analysis, and (in some cases) genome-wide, CRISPR/Cas9 vulnerability screening. The Core works closely with the Molecular Pathology and Genomics Core (Core C) to ensure that samples, models and other reagents are fully characterized. This includes DNA and RNA sequencing, immunophenotyping by traditional methods and by multi-color immunofluorescence, and STR profiling to establish a cost-effective basis for confirming sample fidelity. To facilitate the discovery efforts outlined in the Projects, Core B will pursue 2 Aims.
Aim 1 is to provide Projects 1, 2, and 3 with a pipeline of clinically annotated samples from patients with PTCL on clinical trials, including biopsies pre-treatment, on treatment, and at progression.
Aim 2 is to maintain secured databases of treated patients, patient samples, cell lines, PDXs, and transgenic animals available to Projects 1, 2, and 3. Core B is committed to the principles of open-source utilization. Samples are collected on banking protocols that allow for sharing with external investigators and models are available for distribution around the world. By fully characterizing these resources and then making them available to the research community, Core B markedly amplifies its effect on PTCL research.
The discovery-based efforts outlined in the Projects require access to primary peripheral T-cell lymphomas (PTCLs) and well-characterized cell line, xenograft, and transgenic models of these diseases. Core B will provide a pipeline of genetically-faithful models and clinically-annotated samples from patients with PTCL. The Core will also maintain secured databases of de-identified patient samples, cell lines, patient-derived xenografts, and transgenic animals available to Projects 1, 2, and 3.
